Marine Natural Product Aurilide Activates the OPA1-Mediated Apoptosis by Binding to Prohibitin
Marine Natural Product Aurilide Activates the OPA1-Mediated Apoptosis by Binding to Prohibitin
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DOI：
10.1016/j.chembiol.2010.10.017
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发表时间：
2011-01-28
影响因子：
--
通讯作者：
Uesugi, Motonari
中科院分区：
文献类型：
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作者：
Sato, Shin-ichi;Murata, Asako;Uesugi, Motonari
Aurilide是一种有效的细胞毒性海洋天然产物，可诱导培养的人细胞在皮摩尔至纳摩尔范围内发生凋亡；然而，其作用机制尚不清楚。本研究结果表明，银杏内酯选择性地与线粒体中的禁止蛋白1(PHB1)结合，激活视神经萎缩1(OPA1)的蛋白分解过程，导致线粒体诱导的细胞凋亡。Aurilide的细胞毒性机制表明，PHB1是一种可受小分子调节的细胞凋亡调节蛋白。Aurilide可作为研究线粒体诱导的细胞凋亡的小分子工具。
Aurilide is a potent cytotoxic marine natural product that induces apoptosis in cultured human cells at the picomolar to nanomolar range; however, its mechanism of action has been unknown. Results of the present study showed that aurilide selectively binds to prohibitin 1 (PHB1) in the mitochondria, activating the proteolytic processing of optic atrophy 1 (OPA1) and resulting in mitochondria-induced apoptosis. The mechanism of aurilide cytotoxicity suggests that PHB1 is an apoptosis-regulating protein amenable to modulation by small molecules. Aurilide may serve as a small-molecule tool for studies of mitochondria-induced apoptosis.